Age-Specific Differences in Oncogenic Pathway Deregulation Seen in Human Breast Tumors

Carey K Anders, Chaitanya R Acharya, David S Hsu, Gloria Broadwater, Katherine Garman, John A Foekens, Yi Zhang, Yixin Wang, Kelly Marcom, Jeffrey R Marks, Sayan Mukherjee, Joseph R Nevins, Kimberly L Blackwell and Anil Potti

PLOS ONE, 2008, vol. 3, issue 1, 1-8

Abstract: Purpose: To define the biology driving the aggressive nature of breast cancer arising in young women. Experimental Design: Among 784 patients with early stage breast cancer, using prospectively-defined, age-specific cohorts (young ≤45 years; older ≥65 years), 411 eligible patients (n = 200≤45 years; n = 211≥65 years) with clinically-annotated Affymetrix microarray data were identified. GSEA, signatures of oncogenic pathway deregulation and predictors of chemotherapy sensitivity were evaluated within the two age-defined cohorts. Results: In comparing deregulation of oncogenic pathways between age groups, a higher probability of PI3K (p = 0.006) and Myc (p = 0.03) pathway deregulation was observed in breast tumors arising in younger women. When evaluating unique patterns of pathway deregulation, a low probability of Src and E2F deregulation in tumors of younger women, concurrent with a higher probability of PI3K, Myc, and β-catenin, conferred a worse prognosis (HR = 4.15). In contrast, a higher probability of Src and E2F pathway activation in tumors of older women, with concurrent low probability of PI3K, Myc and β-catenin deregulation, was associated with poorer outcome (HR = 2.7). In multivariate analyses, genomic clusters of pathway deregulation illustrate prognostic value. Conclusion: Results demonstrate that breast cancer arising in young women represents a distinct biologic entity characterized by unique patterns of deregulated signaling pathways that are prognostic, independent of currently available clinico-pathologic variables. These results should enable refinement of targeted treatment strategies in this clinically challenging situation.

Date: 2008
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0001373 (text/html)
https://journals.plos.org/plosone/article/file?id= ... 01373&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0001373

DOI: 10.1371/journal.pone.0001373

Access Statistics for this article

More articles in PLOS ONE from Public Library of Science
Bibliographic data for series maintained by plosone ().